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Title: Understanding polymyalgia rheumatica
Author: Zakout, Samy
ISNI:       0000 0004 5918 1598
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2015
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Polymyalgia rheumatica (PMR) is the commonest rheumatological disease of the elderly white population that is treated with glucocorticoids. Patients suffer with debilitating morning stiffness and pain involving the shoulder girdle and less commonly the pelvic girdle. It has a profound inflammatory response including increased plasma interleukin 6 (IL-6). Our PMR rapid access clinic, established as part of this work, provided material to the 3 studies included in the thesis: The differential diagnosis of PMR is wide, with no consensus amongst clinicians on the use of diagnostic criteria in a clinical context. The diagnosis is made on clinical grounds, reinforced by a positive response to glucocorticoids. By identifying {uncomplicated' PMR patients in our rapid access clinic, I analysed the performance of published diagnostic criteria on our cohort of patients and suggested a new model. Glucocorticoids regimens currently in use vary significantly. There are broadly two regimens: one using a rapid reduction thought to cause less adverse effects with a subsequent greater frequency of disease relapse, and an alternative approach using slow reductions. I measured the relapse rate in the slow reduction regimen we use in our department and found it to be less prevalent than that reported in the literature for rapid reduction. By undertaking 24-hour blood sampling studies in 10 PMR patients, I showed that plasma IL- 6 followed a circadian rhythm in untreated PMR, peaking in the early hours of the morning and correlating with the reported morning stiffness. I performed a small-randomised controlled trial, comparing two treatment arms: morning standard prednisolone (7mg) compared to night timed-release tablet (TRT) prednisone (7mg). The treatment lasted two weeks and was compared to responses after a further 2-week morning prednisolone (15mg). IL-6 and morning stiffness were reduced by all 3 treatments but TRT prednisone was substantially more effective than standard prednisolone, raising the possibility of treating PMR with lower doses of glucocorticoids in the future.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available